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The Indian journal of pediatrics, Volume 75--March, 2008. 210 ORI GI NAL ARTI CLE Spectral analysis of noise in the Neonatal Intensive Care Unit. 229 Homocysteine, Vitamin B 12 and Folate Status in pediatric acute lymphoblastic leukemia.
The Indian journal of pediatrics, Volume 75--March, 2008. 210 ORI GI NAL ARTI CLE Spectral analysis of noise in the Neonatal Intensive Care Unit. 229 Homocysteine, Vitamin B 12 and Folate Status in pediatric acute lymphoblastic leukemia.
The Indian journal of pediatrics, Volume 75--March, 2008. 210 ORI GI NAL ARTI CLE Spectral analysis of noise in the Neonatal Intensive Care Unit. 229 Homocysteine, Vitamin B 12 and Folate Status in pediatric acute lymphoblastic leukemia.
CONTENTS Indian Journal of Pediatrics, Volume 75March, 2008 210 ORI GI NAL ARTI CLES Spectral Analysis of Noise in the Neonatal Intensive Care Unit M.D.Livera, B. Priya, A. Ramesh, P.N. Suman Rao, V. Srilakshmi, M. Nagapoornima, A.G. Ramakrishnan,
M. Dominic and Swarnarekha .. 217 Impact of Parent and Teacher Concordance on Diagnosing Attention Deficit Hyperactivity Disorder and its Sub-types Prahbhjot Malhi, Pratibha Singhi and Manjit Sidhu .. 223 Antithymocyte Globulin and Cyclosporin in Children with Acquired Aplastic Anemia J agdish Chandra, Rahul Naithani, Rakesh Ravi, Varinder Singh, Shashi Narayan,
Sunita Sharma, Harish Pemde and A.K. Dutta .. 229 Homocysteine, Vitamin B 12 and Folate Status in Pediatric Acute Lymphoblastic Leukemia M.N. Sadananda Adiga, Sunil Chandy, Girija Ramaswamy, L. Appaji and Lakshmi Krishnamoorthy .. 235 Growth and Bone Mineralization in Patients with Juvenile Idiopathic Arthritis Ozgur Okumus, Muferet Erguven, Murat Deveci, Oznur Yilmaz and Mine Okumus .. 239 Dapsone Induced Methemoglobinemia : Intermittent vs Continuous Intravenous Methylene Blue Therapy Rajniti Prasad, R. Singh, O.P. Mishra and Madhukar Pandey .. 245 SPECI AL ARTI CLE Doxofylline: The Next Generation Methylxanthine J huma Sankar, Rakesh Lodha and S.K. Kabra .. 251 SYMPOSIUM ON AIIMS PROTOCOLS IN NEONATOLOGY I I I Fluid and Electrolyte Management in Term and Preterm Neonates Deepak Chawla, Ramesh Agarwal, Ashok K. Deorari and Vinod K. Paul .. 255 Sepsis in the Newborn M. J eeva Sankar, Ramesh Agarwal, Ashok K. Deorari and Vinod K. Paul .. 261 Minimal Enteral Nutrition Satish Mishra, Ramesh Agarwal, M. J eevasankar, Ashok K. Deorari and Vinod K. Paul .. 267 Approach to Inborn Errors of Metabolism Presenting in the Neonate Suvasini Sharma, Pradeep Kumar, Ramesh Agarwal, Madhulika Kabra, Ashok K. Deorari and Vinod K. Paul .. 271 Patent Ductus Arteriosus in Preterm Neonates Ramesh Agarwal, Ashok K. Deorari and Vinod K. Paul .. 277 CLI NI CAL BRI EFS Spinal Cord Hamartoma with Pseudopancreatic Cyst Shalu Gupta, Ashok Kumar, A.N. Gangopadhyay and Mohan Kumar .. 281 Page 16 CONTENTS 211 Indian Journal of Pediatrics, Volume 75March, 2008 Page Vesicoureteric Reflux Deterioration in Monozygotic Twins Spyridon Tsiouris, Chrissa Sioka, Anna Marinarou, J ihad Al-Bokharhli, I rene Sionti and Andreas Fotopoulos .. 285 Tay Syndrome S.D. J ambhekar and A.R. Dhongade .. 288 Rosai-Dorfman Disease Madhumita Nandi, R.K. Mondal, Supratim Datta, Balai Chandra Karmakar, K. Mukherjee and T.K. Dhibar .. 290 Langerhans Cell Histiocytosis of Mediastinal Node Urmila N. Khadilkar, A.T.K. Rao, Kausalya Kumari Sahoo and Mukta R. Pai .. 294 Acute Eosinophilic Pneumonia Due to Round Worm Infestation Bindu Aggarwal, Monika Sharma and Tejinder Singh .. 296 NOTES AND NEWS .. 248, 284 AUTHOR FOR GUI DELI NES .. 298 REVI EWERS OF 2007 .. 300 17 Indian Journal of Pediatrics, Volume 75March, 2008 261 Correspondence and Reprint requests : Dr. Vinod K. Paul, Professor, Department of Pediatrics, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India [Received February 7, 2008; Accepted February 7, 2008] Symposium on AIIMS Protocols in Neonatology III Sepsis in the Newborn M. Jeeva Sankar, Ramesh Agarwal, Ashok K Deorari and Vinod K. Paul Division of Neonatology, Department of Pediatrics, All I ndia I nstitute of Medical Sciences, Ansari Nagar, New Delhi, I ndia ABSTRACT Infections are the single largest cause of neonatal deaths globally. According to National Neonatal Perinatal Database (2002- 03), the incidence of neonatal sepsis in India was 30 per 1000 live-births; klebsiella pneumoniae and staphylococcus aureus were the two most common organisms isolated. Based on the onset, neonatal sepsis is classified into two major categories: early onset sepsis, which usually presents with respiratory distress and pneumonia within 72 hours of age and late onset sepsis, that usually presents with septicemia and pneumonia after 72 hours of age. Clinical features of sepsis are non-specific in neonates and a high index of suspicion is required for the timely diagnosis of sepsis. Although blood culture is the gold standard for the diagnosis of sepsis, culture reports would be available only after 48-72 hours. A practical septic screen for the diagnosis of sepsis has been described and some suggestions for antibiotic use have been included in the protocol. [Indian J Pediatr 2008; 75 (3) : 261-266] E-mail: vinodpaul@neonatalhealth.com Key words : Infections; Newborn; Sepsis screen; Antibiotics Sepsis is the commonest cause of neonatal mortality; it is responsible for about 30-50% of the total neonatal deaths in developing countries 1,2 . It is estimated that up to 20% of neonates develop sepsis and approximately 1% die of sepsis related causes 2 . Sepsis related mortality is largely preventable with rational antimicrobial therapy and aggressive supportive care. DEFINITION Neonatal sepsis is a clinical syndrome characterized by signs and symptoms of infection with or without accompanying bacteremia in the first month of life. It encompasses various systemic infections of the newborn such as septicemia, meningitis, pneumonia, arthritis, osteomyelitis, and urinary tract infections. Superficial infections like conjunctivitis and oral thrush are not usually included under neonatal sepsis. EPIDEMIOLOGY: INDIAN DATA The incidence of neonatal sepsis according to the data from National Neonatal Perinatal Database (NNPD, 2002- 03) is 30 per 1000 live births. The database comprising 18 tertiary care neonatal units across India found sepsis to be one of the commonest causes of neonatal mortality contributing to 19% of all neonatal deaths 3 . Septicemia was the commonest clinical category with an incidence of 23 per 1000 live births while the incidence of meningitis was reported to be 3 per 1000 live births. Among intramural births, Klebsiella pneumoniae was the most frequently isolated pathogen (32.5%), followed by Staphylococcus aureus (13.6%). Among extramural neonates (referred from community/other hospitals), Klebsiella pneumoniae was again the commonest organism (27%), followed by Staphylococcus aureus (15%) and Pseudomonas (13%). 3 CLASSIFICATION OF NEONATAL SEPSIS Neonatal sepsis can be classified into two major categories depending up on the onset of symptoms 4 . Early onset sepsis (EOS): It presents within the first 72 hours of life. In severe cases, the neonate may be symptomatic at birth. Infants with EOS usually present with respiratory distress and pneumonia. The source of infection is generally the maternal genital tract. Some maternal / perinatal conditions have been associated with an increased risk of EOS. Knowledge about these potential risk factors would help in early diagnosis of sepsis. Based on the studies from India, the following risk factors seem 67 M.J. Sankar et al 262 Indian Journal of Pediatrics, Volume 75March, 2008 to be associated with an increased risk of early onset sepsis. 4, 5 1. Low birth weight (<2500 grams) or prematurity 2. Febrile illness in the mother with evidence of bacterial infection within 2 weeks prior to delivery. 3. Foul smelling and/or meconium stained liquor. 4. Rupture of membranes >24 hours. 5. Single unclean or > 3 sterile vaginal examination(s) during labor 6. Prolonged labor (sum of 1 st and 2 nd stage of labor > 24 hrs) 7. Perinatal asphyxia (Apgar score <4 at 1 minute) Presence of foul smelling liquor or three of the above mentioned risk factors warrant initiation of antibiotic treatment. Infants with two risk factors should be investigated and then treated accordingly. Late onset sepsis (LOS): It usually presents after 72 hours of age. The source of infection in LOS is either nosocomial (hospital-acquired) or community-acquired and neonates usually present with septicemia, pneumonia or meningitis. 6, 7 Various factors that predispose to an increased risk of nosocomial sepsis include low birth weight, prematurity, admission in intensive care unit, mechanical ventilation, invasive procedures, administration of parenteral fluids, and use of stock solutions. Factors that might increase the risk of community-acquired LOS include poor hygiene, poor cord care, bottle-feeding, and prelacteal feeds. In contrast, breastfeeding helps in prevention of infections. CLINICAL FEATURES Non-specific features: The earliest signs of sepsis are often subtle and nonspecific; indeed, a high index of suspicion is needed for early diagnosis. Neonates with sepsis may present with one or more of the following symptoms and signs (a) Hypothermia or fever (former is more common in preterm low birth weight infants) (b) Lethargy, poor cry, refusal to suck (c) Poor perfusion, prolonged capillary refill time (d) Hypotonia, absent neonatal reflexes (e) Brady/tachycardia (f) Respiratory distress, apnea and gasping respiration (g) Hypo/hyperglycemia (h) Metabolic acidosis. Specific features related to various systems Central nervous system (CNS): Bulging anterior fontanelle, vacant stare, high-pitched cry, excess irritability, stupor/coma, seizures, neck retraction. Presence of these features should raise a clinical suspicion of meningitis. Cardiac: Hypotension, poor perfusion, shock. Gastrointestinal: Feed intolerance, vomiting, diarrhea, abdominal distension, paralytic ileus, necrotizing enterocolitis (NEC). Hepatic: Hepatomegaly, direct hyperbilirubinemia (especially with urinary tract infections). Renal: Acute renal failure. Hematological: Bleeding, petechiae, purpura. Skin changes: Multiple pustules, abscess, sclerema, mottling, umbilical redness and discharge. INVESTIGATIONS Since treatment should be initiated in a neonate suspected to have sepsis without any delay, only minimal and rapid investigations should be undertaken. 8 Blood culture: It is the gold standard for diagnosis of septicemia and should be performed in all cases of suspected sepsis prior to starting antibiotics. A positive blood culture with sensitivity of the isolated organism is the best guide to antimicrobial therapy. Therefore, it is very important to follow the proper procedure for collecting a blood culture. The resident doctor/staff should wear sterile gloves prior to the procedure and prepare a patch of skin approx. 5-cm in diameter over the proposed veni-puncture site. This area should be cleansed thoroughly with alcohol, followed by povidone-iodine, and followed again by alcohol. Povidone-iodine should be applied in concentric circles moving outward from the centre. The skin should be allowed to dry for at least 1 minute before the sample is collected. One-mL sample of blood should be adequate for a blood culture bottle containing 5-10 mL of culture media. Since samples collected from indwelling lines and catheters are likely to be contaminated, cultures should be collected only from a fresh veni-puncture site. All blood cultures should be observed for at least 72 hours before they are reported as sterile. It is now possible to detect bacterial growth within 12-24 hours by using improved bacteriological techniques such as BACTEC and BACT/ALERT blood culture systems. These advanced techniques can detect bacteria at a concentration of 1-2 colony-forming unit (cfu) per mL. Septic screen. 9,10 All neonates suspected to have sepsis should have a septic screen to corroborate the diagnosis. However, the decision to start antibiotics need not be conditional to the sepsis screen result, if there is a strong clinical suspicion of sepsis. The various components of the septic screen include total leukocyte count, absolute neutrophil count, immature to total neutrophil ratio, micro-erythrocyte sedimentation rate and C reactive protein (Table 1). The absolute neutrophil count varies considerably in the immediate neonatal period and normal reference ranges are available from Manroes charts. 11 The lower limit for normal total neutrophil 68 Sepsis in the Newborn Indian Journal of Pediatrics, Volume 75March, 2008 263 counts in the newborn begins at 1800/cmm, rises to 7200/ cmm at 12 hours of age and then declines and persists at 1800/cmm after 72 hours of age. For very low birth weight infants, the reference ranges are available from Mouzinhos charts. 12 The ratio of immature to total neutrophils (I/T ratio) is 0.16 at birth and declines to a peak value of 0.12 after 72 hours of age. Presence of two abnormal parameters in a screen is associated with a sensitivity of 93-100%, specificity of 83%, positive and negative predictive values of 27% and 100% respectively in detecting sepsis. Hence, if two (or more) parameters are abnormal, it should be considered as a positive screen and the neonate should be started on antibiotics. If the screen is negative but clinical suspicion persists, it should be repeated within 12 hours. If the screen is still negative, sepsis can be excluded with reasonable certainty. For early onset sepsis, documentation of polymorphs in the neonatal gastric aspirate at birth could serve as a marker of chorioamnionitis and it may be taken as one parameter of sepsis screen. Lumbar puncture (LP): The incidence of meningitis in neonatal sepsis has varied from 0.3-3% in various studies. 3,6 The clinical features of septicemia and meningitis often overlap; it is quite possible to have meningitis along with septicemia without any specific symptomatology. This justifies the extra precaution of performing LP in neonates suspected to have sepsis. In EOS, lumbar puncture is indicated in the presence of a positive blood culture or if the clinical picture is consistent with septicemia. It is not indicated if antibiotics have been started solely due to the presence of risk factors. In situations of late onset sepsis, LP should be done in all infants prior to starting antibiotics. Lumbar puncture could be postponed in a critically sick neonate. It should be performed once the clinical condition stabilizes. The cerebrospinal fluid characteristics are unique in the newborn period and normal values are given in Table 2. 13 Radiology: Chest X-ray should be considered in the presence of respiratory distress or apnea. An abdominal X-ray is indicated in the presence of abdominal signs suggestive of necrotizing enterocolitis (NEC). Neurosonogram and computed tomography (CT scan) should be performed in all patients diagnosed to have meningitis. Urine culture: In early onset sepsis, urine cultures have a low yield and are not indicated. Urine cultures obtained by suprapubic puncture or bladder catheterization have been recommended in all cases of LOS. Since the procedures are painful and the yield is often poor, we do not recommend a routine urine culture in neonates with sepsis. However, neonates at risk for fungal sepsis and very low birth weight infants with poor weight gain should have a urine examination done to exclude urinary tract infection (UTI). UTI may be diagnosed in the presence of one of the following: (a) >10 WBC/mm 3 in a 10 mL centrifuged sample (b) >10 4 organisms /mL in urine obtained by catheterization and (c) any organism in urine obtained by suprapubic aspiration MANAGEMENT Supportive: Adequate and proper supportive care is crucial in a sick neonate with sepsis. He/she should be nursed in a thermo-neutral environment taking care to avoid hypo/ hyperthermia. Oxygen saturation should be maintained in the normal range; mechanical ventilation may have to be initiated if necessary. If the infant is hemodynamically unstable, intravenous fluids should be administered and the infant is to be monitored for hypo/hyperglycemia. Volume expansion with crystalloids/colloids and judicious use of inotropes are essential to maintain normal tissue perfusion and blood pressure. Packed red cells and fresh frozen plasma might have to be used in the event of anemia or bleeding diathesis. Antimicrobial therapy: There cannot be a single recommendation for the antibiotic regimen of neonatal sepsis for all settings. The choice of antibiotics depends on the prevailing flora in the given unit and their antimicrobial sensitivity. This protocol does not aim to provide a universal recommendation for all settings but lays down broad guidelines for the providers to make a rational choice of antibiotic combination. Decision to start antibiotics is based upon clinical features and/ or a positive septic screen. However duration of antibiotic therapy is dependent upon the presence of a positive blood culture and meningitis (Table 3). Indications for Starting Antibiotics: The indications for starting antibiotics in neonates at risk of EOS include any one of the following: TABLE 1. A Practical Sepsis Screen Components Abnormal value Total leukocyte count <5000/mm 3 Absolute neutrophil count Low counts as per Manroe chart 11 for term and Mouzinhos chart 12 for VLBW infants Immature/total neutrophil >0.2 Micro-ESR >15 mm in 1st hour C reactive protein (CRP) >1 mg/dL (ESR, erythrocyte sedimentation rate) TABLE 2. Normal Cerebrospinal Fluid Examination in Neonates 13 CSF Components Normal range Cells/mm3 8 (0-30 cells) PMN (%) 60% CSF protein (mg/dL) 90 (20-170) CSF glucose (mg/dL) 52 (34-119) CSF/ blood glucose (%) 51 (44-248) (PMN, polymorphonuclear cells; CSF, cerebrospinal fluid) 69 M.J. Sankar et al 264 Indian Journal of Pediatrics, Volume 75March, 2008 (a) presence of 3 risk factors for early onset sepsis (see above) (b) presence of foul smelling liquor (c) presence of 2 antenatal risk factor(s) and a positive septic screen and (d) strong clinical suspicion of sepsis. The indications for starting antibiotics in LOS include: (a) positive septic screen and/or (b) strong clinical suspicion of sepsis. (Fig. 1) Prophylactic Antibiotics: We do not use prophylactic antibiotics in the following circumstances: infants on IV fluids/TPN, meconium aspiration syndrome, and after exchange transfusion(s). An exchange transfusion conducted under strict asepsis (single use catheter, sterile gloves, removal of catheter after the procedure) does not increase the risk of sepsis and hence does not merit antibiotics. However, a messy exchange transfusion could be treated with prophylactic antibiotics. In our unit, ventilated neonates are treated with prophylactic antibiotics for 5-7 days. Choice of antibiotics: Empirical antibiotic therapy should be unit-specific and determined by the prevalent spectrum of etiological agents and their antibiotic sensitivity pattern. Antibiotics once started should be TABLE 3. Duration of Antibiotic Therapy in Neonatal Sepsis Diagnosis Duration Meningitis (with or without positive blood/ 21 days CSF culture) Blood culture positive but no meningitis 14 days Culture negative, sepsis screen positive and 7-10 days clinical course consistent with sepsis Culture and sepsis screen negative, but 5-7 days clinical course compatible with sepsis Fig. 1. Protocol for sepsis 70 Sepsis in the Newborn Indian Journal of Pediatrics, Volume 75March, 2008 265 modified according to the sensitivity reports. Guidelines for empirical antibiotic therapy have been provided in Table 4. The empirical choice of antibiotics is dependent upon the probable source of infection. For infections that are likely to be community-acquired where resistant strains are unlikely, a combination of ampicillin or penicillin with gentamicin may be a good choice as a first line therapy. TABLE 4. Empirical Choice of Antibiotics for Treatment of Neonatal Sepsis Clinical situation Septicemia & Meningitis Pneumonia FIRST LINE Penicillin or Ampicillin and Gentamicin Add Cefotaxime Community-acquired (Resistant strains are unlikely) SECOND LINE Ampicillin or Cloxacillin and Add Cefotaxime Hospital-acquired (Some strains Gentamicin or Amikacin are likely to be resistant) THIRD LINE Cefotaxime or Piperacillin-Tazobactam or Hospital-acquired sepsis (Most Ciprofloxacin Same (Avoid Ciprofloxacin) strains are likely to be resistant) andAmikacin; Consider Vancomycin if MRSA is suspected. TABLE 5. Drugs, Route of Administration and Doses of Common Antibiotics Used. Drug Route Birth Weight 2000g Birth Weight >2000g 0-7 d >7 days 0-7 days >7 days Amikacin I/V, I/M 7.5 q12h 7.5 q8h 10 q12h 10 q8h Ampicillin Meningitis I/V 100 q12h 100 q8h 100 q 8h 100 q6h Others I/V, I/M 25 q12h 25 q8h 25 q8h 25 q6h Cefotoxime Meningitis I/V 50 q6h 50 q6h 50 q6h 50 q6h Others I/M, I/V 50 q12h 50 q8h 50 q12h 50 q8h Piperacillin+ I/V 50-100 q12h 50-100 q8h 50-100 q12h 50-100 q12h Tazobactam Ceftriaxone I/M, I/V 50 q24h 50 q24h 50 q24h 75 q24h Ciprofloxacin I/V, PO 10-20 q24h 10-20 q24h 10-20 q12h 10-20 q12h Cloxacillin Meningitis I/V 50 q12h 50 q8h 50 q8h 50 q6h Others I/V 25 q12h 25 q8h 25 q8h 25 q6h Gentamicin Conventional I/V, I/M 2.5 q12h 2.5 q8h 2.5 q12h 2.5 q8h Single dose I/M 4 q24 h 4 q24 hr 5 q24h 5 q24h Netilmicin I/V, I/M 2.5 q12h 2.5 q8h 2.5 q12h 2.5 q8h Penicillin G (units/kg/dose) Meningitis I/V 75,000 q12h 75,000 q8h 75,000 q8h 75,000 q6h -100,000 -1,00,000 -1,00,000 -1,00,000 Others I/V, I/M 25,000 q12h 25,000 q8h 25,000 q8h 25,000 q6h Vancomycin I/V 15 q12h 15 q8h 15 q12h 15 q8h All doses are in mg/kg/dose; (I/V, intravenous; I/M, intramuscular; PO, per-oral; h, hourly) Protocol for sepsis For infections that are acquired during hospital stay, resistant pathogens are likely and a combination of ampicillin or cloxacillin with gentamicin or amikacin may be instituted. In nurseries where this combination is ineffective due to the presence of multiple resistant strains of klebsiella and other gram-negative bacilli, a combination of a third generation cephalosporin (cefotaxime or ceftazidime) with amikacin may be appropriate. 3 rd generation cephalosporins have very 71 M.J. Sankar et al 266 Indian Journal of Pediatrics, Volume 75March, 2008 good CSF penetration and are traditionally thought to have excellent antimicrobial activity against gram negative organisms. Hence they were considered to be a good choice for the treatment of nosocomial infections and meningitis. However, recent reports suggest that at least 60-70% of the gram-ve organisms are resistant to them. 14-16 More over, routine use of these antibiotics might increase the risk of infections with ESBL (extended spectrum beta-lactamase) positive organisms. Therefore it is preferable to use antibiotics such as piperacillin- tazobactam or methicillin/vancomycin in units with high incidence of resistant strains. A combination of piperacillin-tazobactam with amikacin should be considered if pseudomonas sepsis is suspected. Penicillin resistant staphylococcus aureus should be treated with cloxacillin, nafcillin or methicillin. Addition of an aminoglycoside is useful in therapy against staphylococcus. Methicillin resistant staphylococcus aureus (MRSA) should be treated with a combination of ciprofloxacin or vancomycin with amikacin. Ciprofloxacin has excellent activity against gram-negative organisms also; however, it does not have good CSF penetration. It may be used for the treatment of resistant gram-negative bacteremia after excluding meningitis. For sepsis due to enterococcus, a combination of ampicillin and gentamicin is a good choice for initial therapy. Vancomycin should be used for the treatment of enterococcus resistant to the first line of therapy. The dosage, route, and frequency of commonly used antimicrobial agents are given in table 5. Reserve antibiotics: Newer antibiotics like aztreonam, meropenem and imipenem are also now available in the market. Aztreonam has excellent activity against gram- negative organisms while meropenem is effective against most bacterial pathogens except methicillin resistant staphylococcus aureus (MRSA) and enterococcus. Imipenem is generally avoided in neonates because of the reported increase in the incidence of seizures following its use. Empirical use of these antibiotics should be avoided; they should be reserved for situations where sensitivity of the isolated organism warrants their use. Adjunctive therapy Exchange transfusion (ET): Sadana et al 17 have evaluated the role of double volume exchange transfusion in septic neonates with sclerema and demonstrated a 50% reduction in sepsis related mortality in the treated group. We perform double-volume exchange transfusion with cross-matched fresh whole blood as adjunctive therapy in septic neonates with sclerema. Intravenous Immunoglobulin (IVIG): Non-specific pooled IVIG has not been found to be useful. 18 Granulocyte-Macrophage colony stimulating factor (GM- CSF): This mode of treatment is still experimental. 19 REFERENCES 1. Bang AT, Bang RA, Bactule SB, Reddy HM, Deshmukh MD. Effect of home-based neonatal care and management of sepsis on neonatal mortality: field trial in rural India. Lancet 1999; 354 : 1955-19861. 2. Stoll BJ. The global impact of neonatal infection. Clin Perinatol 1997; 24 : 1-21. 3. Report of the National Neonatal Perinatal Database (National Neonatology Forum) 2002-2003. 4. 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